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Emory Vaccine Research Center study identifies specific gene required for long-term immunity

In a study in the Jan. 16 issue of Nature, scientists at the Emory Vaccine Research Center show that a gene called SAP is required to generate long-term immunity.

By measuring the immune responses of "knockout" mice genetically engineered to lack SAP, researchers found that the gene's absence impairs the immune system's "memory," namely its ability to recognize and react to infection. This finding has implications for research in vaccines, which by definition must engender long-term immunity.

SAP recently was identified as the gene responsible for a lethal human genetic disease, X-linked lymphoproliferative disease.

"There are only a few known lethal immunodeficiencies in humans, and a defect in the SAP gene is one of them," said first author Shane Crotty, Ph.D. "So this gene is clearly important for immune responses. Our work now shows that the SAP gene is a central player in long-term antibody responses, and indicates that manipulation of SAP may have therapeutic benefits in generating better antibody responses."

Crotty and his colleagues compared the immune responses of the knockout mice against those of genetically normal control mice. When infected with a virus, in this case lymphocytic choriomeningitis virus, both sets of mice mounted initial immune responses of similar magnitude. After the initial response subsided, however, the SAP-negative mice failed to produce significant numbers of either virus-specific plasma cells or memory B-cells, both of which are crucial components of long-term immunity.

In the Nature paper, the investigators commented that it is unusual to find that a gene affects long-term but not short-term immunity.

"What is so interesting about this gene is that it controls the generation of long-term memory, but it's not important for short-term immune responses. We haven't seen a gene that does this before," said Rafi Ahmed, Ph.D., VRC Director and senior author of the study.

The researchers were able
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
15-Jan-2003


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